Abstract
The objective of this study was to examine if (R)-methanandamide, a metabolically stable chiral analog of the endogenous ligand anandamide, is a cannabimimetic with a lower efficacy than Δ9-THC. Employing a two-lever choice drug discrimination procedure, rats were trained to discriminate between 1.8, 3.0, or 5.6 mg/kg Δ9-tetrahydrocannabinol (Δ9-THC) and vehicle. Different training doses were used in order to create assays with different efficacy demands. Generalization tests with 18 mg/kg (R)-methanandamide yielded around 90% Δ9-THC responses in the two lower Δ9-THC training dose conditions. However, only around 60% Δ9-THC responses occurred in the 5.6 mg/kg Δ9-THC training dose condition in tests with 18 mg/kg (R)-methanandamide; a higher dose (30 mg/kg) produced even fewer Δ9-THC-appropriate responses in this group. Morphine did not substitute for Δ9-THC. In conclusion, the data with Δ9-THC and (R)-methanandamide indicate that cannabinoid agonists can have varying degrees of intrinsic activity at a receptor site, or may produce their behavioral actions through multiple mechanisms, or both.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received: 9 May 1998 / Final version: 28 May 1998
Rights and permissions
About this article
Cite this article
Järbe, T., Lamb, R., Makriyannis, A. et al. Δ9-THC training dose as a determinant for (R)-methanandamide generalization in rats. Psychopharmacology 140, 519–522 (1998). https://doi.org/10.1007/s002130050797
Issue Date:
DOI: https://doi.org/10.1007/s002130050797